Julie S. Haas

Measuring spike train synchrony

Estimating the degree of synchrony or reliability between two or more spike trains is a frequent task in both experimental and computational neuroscience. In recent years, many different methods have been proposed that typically compare the timing of spikes on a certain time scale to be optimized by the analyst. Here, we propose the ISI-distance, a simple complementary approach that extracts information from the interspike intervals by evaluating the ratio of the instantaneous firing rates. The method is parameter free, time scale independent and easy to visualize as illustrated by an application to real neuronal spike trains obtained in vitro from rat slices. In a comparison with existing approaches on spike trains extracted from a simulated Hindemarsh-Rose network, the ISI-distance performs as well as the best time-scale-optimized measure based on spike timing.

Activity-Dependent Long-Term Depression of Electrical Synapses

Paired bursting in coupled neurons depresses electrical synapses while their asymmetry increases after unidirectional use. Use-dependent forms of synaptic plasticity have been extensively characterized at chemical synapses, but a relationship between natural activity and strength at electrical synapses remains elusive. The thalamic reticular nucleus (TRN), a brain area rich in gap-junctional (electrical) synapses, regulates cortical attention to the sensory surround and participates in shifts between arousal states; plasticity of electrical synapses may be a key mechanism underlying these processes. We observed long-term depression resulting from coordinated burst firing in pairs of coupled TRN neurons. Changes in gap-junctional communication were asymmetrical, indicating that regulation of connectivity depends on the direction of use. Modification of electrical synapses resulting from activity in coupled neurons is likely to be a widespread and powerful mechanism for dynamic reorganization of electrically coupled neuronal networks.

Inhibitory synaptic plasticity: spike timing-dependence and putative network function

While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

Measuring multiple spike train synchrony.

Measures of multiple spike train synchrony are essential in order to study issues such as spike timing reliability, network synchronization, and neuronal coding. These measures can broadly be divided in multivariate measures and averages over bivariate measures. One of the most recent bivariate approaches, the ISI-distance, employs the ratio of instantaneous interspike intervals (ISIs). In this study we propose two extensions of the ISI-distance, the straightforward averaged bivariate ISI-distance and the multivariate ISI-diversity based on the coefficient of variation. Like the original measure these extensions combine many properties desirable in applications to real data. In particular, they are parameter-free, time scale independent, and easy to visualize in a time-resolved manner, as we illustrate with in vitro recordings from a cortical neuron. Using a simulated network of Hindemarsh-Rose neurons as a controlled configuration we compare the performance of our methods in distinguishing different levels of multi-neuron spike train synchrony to the performance of six other previously published measures. We show and explain why the averaged bivariate measures perform better than the multivariate ones and why the multivariate ISI-diversity is the best performer among the multivariate methods. Finally, in a comparison against standard methods that rely on moving window estimates, we use single-unit monkey data to demonstrate the advantages of the instantaneous nature of our methods.

State-dependent modulation of gap junction signaling by the persistent sodium current.

Thalamic neurons fluctuate between two states: a hyperpolarized state associated with burst firing and sleep spindles, and a depolarized state associated with tonic firing and rapid, reliable information transmission between the sensory periphery and cortex. The thalamic reticular nucleus (TRN) plays a central role in thalamocortical processing by providing feed-forward and feedback inhibition to thalamic relay cells; TRN cells participate in the generation of sleep spindles, and have been suggested to focus the neural “searchlight” of attention. The mechanisms underlying synchrony in the TRN during different behavioral states are largely unknown. TRN cells are densely interconnected by electrical synapses. Here we show that activation of the persistent sodium current (INaP) by depolarization causes up to fourfold changes in electrical synaptic efficacy between TRN neurons. We further show that amplification of electrical synaptic responses strongly enhances tonic spike synchrony but, surprisingly, does not affect burst coordination. We use a Hodgkin–Huxley model to gain insight into the differences between the effects of burstlets, spikelets, and amplification on burst and spike times.

Bursts modify electrical synaptic strength

Changes in synaptic strength resulting from neuronal activity have been described in great detail for chemical synapses, but the relationship between natural forms of activity and the strength of electrical synapses had previously not been investigated. The thalamic reticular nucleus (TRN), a brain area rich in gap junctional (electrical) synapses, regulates cortical attention, initiates sleep spindles, and participates in shifts between states of arousal. Plasticity of electrical synapses in the TRN may be a key mechanism underlying these processes. Recently, we demonstrated a novel activity-dependent form of long-term depression of electrical synapses in the TRN (Haas et al., 2011). Here we provide an overview of those findings and discuss them in broader context. Because gap junctional proteins are widely expressed in the mammalian brain, modification of synaptic strength is likely to be a widespread and powerful mechanism at electrical synapses throughout the brain.

Activity-dependent plasticity of electrical synapses: Increasing evidence for its presence and functional roles in the mammalian brain

Gap junctions mediate electrical synaptic transmission between neurons. While the actions of neurotransmitter modulators on the conductance of gap junctions have been extensively documented, increasing evidence indicates they can also be influenced by the ongoing activity of neural networks, in most cases via local interactions with nearby glutamatergic synapses. We review here early evidence for the existence of activity-dependent regulatory mechanisms as well recent examples reported in mammalian brain. The ubiquitous distribution of both neuronal connexins and the molecules involved suggest this phenomenon is widespread and represents a property of electrical transmission in general.

Asymmetry and modulation of spike timing in electrically coupled neurons

Electrical coupling mediates interactions between neurons of the thalamic reticular nucleus (TRN), which play a critical role in regulating thalamocortical and corticothalamic communication by inhibiting thalamic relay cells. Accumulating evidence has shown that asymmetry of electrical synapses is a fundamental and dynamic property, but the effect of asymmetry on coupled networks is unexplored. Recording from patched pairs in rat brain slices, we investigate asymmetry in the subthreshold regime and show that electrical synapses can exert powerful effects on the spike times of coupled neighbors. Electrical synaptic signaling modulates spike timing by 10-20 ms, in an effect that also exhibits asymmetry. Furthermore, we show through modeling that coupling asymmetry expands the set of outputs for pairs of coupled neurons through enhanced regions of synchrony and reversals of spike order. These results highlight the power and specificity of signaling exerted by electrical synapses, which contribute to information flow across the brain.

A calcium-dependent pathway underlies activity-dependent plasticity of electrical synapses in the thalamic reticular nucleus

Electrical synapses are modified by various forms of activity, including paired activity in coupled neurons and tetanization of the input to coupled neurons. We show that plasticity of electrical synapses that results from paired spiking activity in coupled neurons depends on calcium influx and calcium‐initiated signalling pathways. Plasticity that results from tetanization of input fibres does not depend on calcium influx or dynamics. These results imply that electrically coupled neurons have distinct sets of mechanisms for adjusting coupling according to the specific type of activity they experience.

Measuring spike train synchrony and reliability

Estimating the degree of synchrony or reliability between two or more spike trains is a frequent task in both experimental and computational neuroscience. In recent years, many different methods have been proposed that typically compare the timing of spikes on a certain time scale to be fixed beforehand. In this study [1], we propose the ISI-distance, a simple complementary approach that extracts information from the interspike intervals by evaluating the ratio of the instantaneous frequencies. The method is parameter free, time scale independent and easy to visualize as illustrated by an application to real neuronal spike trains obtained in vitro from rat slices (cf. [2]). We compare the method with six existing approaches (two spike train metrics [3,4], a correlation measure [2,5], a similarity measure [6], and event synchronization [7]) using spike trains extracted from a simulated Hindemarsh-Rose network [8]. In this comparison the ISI-distance performs as well as the best time-scale-optimized measure based on spike timing, without requiring an externally determined time scale for interaction or comparison.